Astragaloside IV attenuates myocardial fibrosis by inhibiting TGF-β1 signaling in coxsackievirus B3-induced cardiomyopathy

被引：99

作者：

Chen, Ping ^{[1
,2
]}

Xie, Yeqing ^{[1
]}

Shen, E. ^{[1
]}

Li, Gary G. ^{[2
]}

Yu, Yong ^{[1
]}

Zhang, Cassie B. ^{[2
]}

Yang, Yingzhen ^{[1
]}

Zou, Yunzeng ^{[1
]}

Ge, Junbo ^{[1
]}

Chen, Ruizhen ^{[1
]}

Chen, Haozhu ^{[1
]}

机构：

[1] Fudan Univ, Zhongshan Hosp, Shanghai Inst Cardiovasc Dis, Minist Publ Hlth,Key Lab Viral Heart Dis, Shanghai 200032, Peoples R China

[2] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2011年 / 658卷 / 2-3期

基金：

高等学校博士学科点专项科研基金; 中国国家自然科学基金;

关键词：

Astragaloside IV; Myocardial fibrosis; Dilated cardiomyopathy; TGF-beta; 1; Coxsackievirus B3; Viral myocarditis; CARDIAC-FUNCTION; GROWTH-FACTOR; HEART; COLLAGEN; MEMBRANACEUS; MECHANISMS; INCREASE; DISEASE; MURINE; CELLS;

D O I：

10.1016/j.ejphar.2011.02.040

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Myocardial fibrosis plays an important role in coxsackievirus B3 (CVB3) induced dilated cardiomyopathy. Excessive transforming growth factor (TGF)-beta 1 contributes to a pathologic excess of tissue fibrosis. We investigated the effect of astragaloside IV on myocardial fibrosis in CVB3-induced dilated cardiomyopathy. BALB/c mice were inoculated with CVB3 to induce acute viral myocarditis on day 7 (acute VMC group), monthly for 3 months to induce chronic myocarditis (chronic VMC group), and monthly for 9 months to induce dilated cardiomyopathy (DCM group). The same method was used for the DCM+Astra group as that of the DCM group, but former group was given with astragaloside IV-containing drinking water. Compared to DCM group, astragaloside IV treatment significantly increased the survival rate. Histological findings and the collagen volume fraction showed that astragaloside IV decreased fibrosis in heart tissues. Astragaloside IV decreased the level of the serum carboxy-terminal propeptide of procollagen type I (PICP) and the ratio of PICP/N-terminal type I procollagen propeptide (PINP). Ameliorated myocardial fibrosis was consistent with the downregulated expression of TGF-beta 1 and its downstream pSmad2/3 and Smad4 in the myocardium of the DCM+Astra group compared to the DCM group. The level of type I collagen was lower in the DCM+Astra group than the DCM group. The same effect was found in the in vitro study. These findings showed that astragaloside IV had a potent preventive effect on myocardial fibrosis in CVB3-induced dilated cardiomyopathy that might be due to downregulation of TGF-beta 1-Smad signaling. Crown Copyright (C) 2011 Published by Elsevier B.V. All rights reserved.

引用

页码：168 / 174

页数：7

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